Macrophage scavenger receptor 1, a suppressor of HIV infection, is down-regulated in transgender females

Transgender people are at greater risk than cisgender people of acquiring HIV and other sexually transmitted infections. Globally, the risk of acquiring HIV infection is nearly 49 times higher in transgender women than in other populations. Although behavioral and psychosocial factors contribute to the higher HIV risk in transgender people, gender-affirming hormone (GAH) (i.e., testosterone for transgender individuals assigned female at birth or estrogen/antiandrogen for transgender individuals assigned male at birth) may alter immune cell functions, resulting in increased HIV transmission. We have profiled gene expression of PBMCs from transgender females and males and have identified four specific genes (MTND1P23, IGSF10, MSR1, and DUXAP9) that were differentially expressed in transgender females. Among these genes, macrophage scavenger receptor 1 was down-regulated 0.5- or 0.4-fold compared to cis females and cis males, respectively. Transient expression of MSR1 suppressed in vitro HIV infection, suggesting that MSR1 protects cells against HIV. The data indicate that down-regulation of MSR1 in transgender women may play a role in their increased HIV risk. Future studies on the mechanisms by which MRS1 inhibits HIV infection may offer new strategies for HIV prevention in transgender women. NIH R21AI55322